BB-10901 in Treating Patients With Relapsed or Refractory Solid Tumors

Sponsor

ImmunoGen, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00346385

Collaborator

(none)

Enrollment

Locations

115

Duration (Months)

10.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as BB-10901, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase I trial is studying the side effects and best dose of BB-10901 in treating patients with relapsed or refractory solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Merkel Cell Carcinoma SCLC	Drug: BB-10901	Phase 1

Detailed Description

OBJECTIVES:

Primary

Determine the safety and tolerability of BB-10901
Determine the maximum tolerated dose of this drug in these patients.

Secondary

Determine the pharmacokinetics of this drug in these patients.
Determine the efficacy of this drug in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Patients receive BB-10901 IV over 40 minutes once daily on days 1-3.* Treatment repeats every 21 days

NOTE: *Patients who do not tolerate 3 consecutive daily infusions of BB-10901 may receive infusions of BB-10901 on 3 alternate days, upon approval by the investigator and/or the independent Safety Review Board.

Cohorts of 4-6 patients receive escalating doses of BB-10901 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 4-6 patients experience dose-limiting toxicity in course 1. Up to 40 patients are treated at the MTD.

After completion of study treatment, patients are followed for short term and long term follow up and survival.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued to this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

97 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Open-Label, Dose Escalation Study of Daily Dosing With BB-10901

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Outcome Measures

Primary Outcome Measures

Safety and tolerability assessed by toxicity evaluation and prothrombin time assessments [these tests will be conducted at various timepoints during a patients participation in the trial]

Secondary Outcome Measures

Pharmacokinetics assessed by measuring intact conjugate and total huN901 antibody concentration for each time point and dose level [PK is assessed during the first cycle (21 days) of a patients participation]
Efficacy assessed by measuring response (complete or partial response) and biomarker levels of neuron-specific enolase and soluble neural cell adhesion molecules (NCAM) [efficacy is assessed every 2 cycles during a patients participation while other blood tests are taken during every cycle]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS During Dose Escalation:

Histologically or cytologically confirmed diagnosis of 1 of the following:
Small cell lung cancer (SCLC)
Other pulmonary tumors of neuroendocrine origin, including neuroendocrine carcinoma or non-SCLC with neuroendocrine features
Non-pulmonary small cell carcinoma
Metastatic carcinoid tumor
Other CD56-positive solid tumor
Diagnoses other than SCLC must have confirmation of tumor CD56 expression before study entry
Relapsed or refractory disease
Must have received at least 1 but no more than 3 prior chemotherapy regimens* and recovered from any acute toxicities
No prior chemotherapy for carcinoid or neuroendocrine tumors

DISEASE CHARACTERISTICS During MTD Expansion:

Relapsed or refractory Small cell lung cancer (SCLC)
Metastatic Merkel Cell carcinomas
Ovarian carcinomas

At the MTD:

SCLC patients must have received one, but no more than 1 prior chemotherapy regimen Merkel and Ovarian patients must have received at least one prior chemotherapy regimen. Ovarian patients must have received at least one platinum-based regimen.

Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
No uncontrolled carcinoid syndrome (e.g., flushing, uncontrolled diarrhea, labile blood pressure)
No active brain metastases; no evidence of active disease and no requirement for anticonvulsant medications or steroids.

PATIENT CHARACTERISTICS:

Life expectancy ≥ 3 months
ECOG performance status 0-2
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL
Creatinine ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Bilirubin ≤ 3 times ULN
No rapidly rising liver function tests (LFTs)
Pancreatic function, amylase and lipase within upper limit of normal.
No significant residual neurological or cardiac toxicity ≥ grade 2 after prior chemotherapy
No myocardial infarction within the past 6 months
No unstable angina pectoris
No uncontrolled congestive heart failure
No uncontrolled arrhythmia
No severe aortic stenosis
No history of multiple sclerosis or other demyelinating disease
No Eaton-Lambert syndrome (para-neoplastic syndrome)
No history of hemorrhagic stroke
No CNS injury with residual neurologic deficit
No ischemic stroke within the past 6 months
No history of pancreatitis
No current active infection or history of recurrent infection with varicella-zoster virus (shingles) or cytomegalovirus
No other concurrent serious infection
No chronic alcoholism
No other concurrent illness or condition that would interfere with study outcome
No other malignancy within the past 3 years except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
No known recent biochemical or clinical evidence of pancreatitis or extensive metastatic disease involving the pancreas

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Total cumulative dosage of prior anthracycline treatment must not exceed threshold for cardiotoxicity
No known hypersensitivity to previous monoclonal antibody therapy
More than 4 weeks since prior and no concurrent chemotherapy or radiotherapy
More than 4 weeks since prior and no other concurrent investigational agents
At least 4 weeks since prior and no concurrent surgery
No other concurrent antineoplastic treatment, including immunotherapy or steroid therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94115
2	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
3	The Ohio State University Cancer Center and Research Institute	Columbus	Ohio	United States
4	Oklahoma University	Oklahoma City	Oklahoma	United States	73104
5	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
6	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1023
7	Christie Hospital NHS Trust	Manchester	England	United Kingdom	M20 9BX
8	Cancer Research Centre at Weston Park Hospital	Sheffield	England	United Kingdom	S1O 2SJ
9	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England	United Kingdom	SM2 5PT